Laboratory rabbits may be HIV infected by administration of a single dose of infected human T cells. Recent studies of this potential animal model for AIDS have taken several new directions. PCR analysis of samples from rabbits taken at necropsy showed that brain, spleen and other lymphoid tissues are heavily infected, whereas other tissues, such as liver, do not contain detectable levels of viral DNA or RNA. Peripheral blood lymphocytes from infected rabbits were tested for HIV-1 infection, but virus was not detected until approximately 25 weeks post-infection. Attempts to hasten this time are being made. An improved PCR reaction has increased sensitivity and a systematic study of the synergy of HTLV-I superinfection with HIV-1 infection has been carried out. Most promising have been experiments in which lymphoid tissues from rabbits infected for long periods of time were passaged to uninfected rabbits. The recipients showed the appearance of virus in peripheral cells as early as six weeks following administration of spleen cells from a rabbit that had been infected with HIV-1 for two years previously. A study of the production of the regulatory protein, nef, indicated that about 15% of infected animals made antibody to it. In vitro studies of infection of rabbit cell lines have focused on the nef gene transcripts and protein produced in the rabbit cell lines, and compared to those produced in human cells infected with the same viral stocks. It was shown that nef and other regulatory messages are present in very low amounts in the rabbit cells relative to the human. Attempts will be made to carry out transfections with constructs making the regulatory proteins in order to determine whether increased production of these may enhance the infection process in the rabbit. It is anticipated that in vitro results will have an impact upon future use of the rabbit infection model. For example, one may consider the use of a transgenic rabbit expressing HIV regulatory proteins in a tissue specific manner.